Crosstalk between gut and brain has long been appreciated in health and disease, and the gut microbiota is a key player in communication between these two distant organs. Yet, the mechanisms through which the microbiota influences development and function of the gut–brain axis remain largely unknown. Barriers present in the gut and brain are specialized cellular interfaces that maintain strict homeostasis of different compartments across this axis. These barriers include the gut epithelial barrier, the blood–brain barrier and the blood–cerebrospinal fluid barrier. Barriers are ideally positioned to receive and communicate gut microbial signals constituting a gateway for gut–microbiota–brain communication. In this Review, we focus on how modulation of these barriers by the gut microbiota can constitute an important channel of communication across the gut–brain axis. Moreover, barrier malfunction upon alterations in gut microbial composition could form the basis of various conditions, including often comorbid neurological and gastrointestinal disorders. Thus, we should focus on unravelling the molecular and cellular basis of this communication and move from simplistic framing as ‘leaky gut’. A mechanistic understanding of gut microbiota modulation of barriers, especially during critical windows of development, could be key to understanding the aetiology of gastrointestinal and neurological disorders.

肠道和大脑之间的串扰长期以来在健康和疾病方面受到重视，肠道微生物群是这两个遥远器官之间沟通的关键参与者。然而，微生物群影响肠脑轴发育和功能的机制仍然很大程度上未知。肠道和大脑中存在的屏障是专门的细胞界面，可维持该轴上不同区室的严格稳态。这些屏障包括肠上皮屏障、血脑屏障和血脑脊液屏障。屏障的位置非常理想，可以接收和传达肠道微生物信号，构成肠道-微生物群-大脑沟通的门户。在这篇综述中，我们重点关注肠道微生物群对这些屏障的调节如何构成跨肠-脑轴的重要沟通渠道。此外，肠道微生物组成改变导致的屏障功能障碍可能构成各种疾病的基础，包括通常合并的神经和胃肠道疾病。因此，我们应该集中精力揭示这种通讯的分子和细胞基础，并摆脱“肠漏”的简单化框架。对肠道微生物群调节屏障的机制的了解，尤其是在发育的关键窗口期，可能是了解胃肠道和神经系统疾病的病因学的关键。